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Drug Metabolism and Pharmacokinetics Core. Goal: To provide comprehensive pharmacology support for preclinical and clinical research. Services:. Pharmacokinetic studies: Quantify drug levels in serum/plasma, tissue or cells

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drug metabolism and pharmacokinetics core
Drug Metabolism and Pharmacokinetics Core

Goal: To provide comprehensive pharmacology support for preclinical and clinical research

services
Services:
  • Pharmacokinetic studies: Quantify drug levels in serum/plasma, tissue or cells
  • Evaluation of Organ Toxicity: Blood chemistry analysis for liver, kidney and bone marrow toxicity
  • Hematology: Measure complete blood counts
  • Measure GSH/GSSG
  • Redox analysis: Detection of protein thiol status in cells, tissue, serum and plasma.
  • Education and training
nov 002 a myeloproliferative agent

NOV-002, a myeloproliferative agent

Phase II: Neo-adjuvant breast cancer trial at MUSC

slide5

A.

ug/mL GSSG

B.

ug/mL GSH

slide6

Estimated pharmacokinetic parameters for NOV-002 (GSSG) and its primary metabolite (GSH)

PK ParameterGSH GSSG

Co (ug/mL) 4.10 0.65

Cmax (ug/mL) 18.30 2.16

Tmax (hr) 0.16 0.15

Volume of distribution, V/F (L/kg) 42.61

K01 (absorption rate constant), hr-1 6.42

K10 (elimination rate constant), hr-15.81 6.40

AUC 0-30min (ug.h/mL)6.37 1.18

Clearance, CL/F (L/hr/kg) 273.15

slide8

Table 2. Mortality and Nephrotoxicity of Cisplatin in Mice

  • Elevated Abnormal
  • Mortality Creatinine Renal Histology
  • Saline 0/6* 0/6 0/6
  • NOV-002 0/6 0/6 0/6
  • Cisplatin 1/8§ 6/7§ 7/7§
  • Cisplatin + NOV-002 0/9 3/9 3/9
  • Data are the number of mice who died, had elevated plasma creatinine (>0.2 mg/dL) or abnormal renal histology over the number of mice treated.
  • § Statistically significant differences between treatment groups were detected with a Fisher Exact Test, P<0.01.
slide9

Saline NOV-002

Cisplatin Cisplatin + NOV-002

cisplatin induced bone marrow toxicity white blood cells

Normal 6 x 109

Female +/+

x 109 cells/mL

Female Male

Cisplatin + +

NOV-002 - +

Cisplatin Induced Bone Marrow ToxicityWhite Blood Cells
  • HM2 Hematology System (Abaxis)
redox analysis

-S-TGTM

+ TGTM

-SH

-S-SG

+

NOV-002

Redox analysis:

*

*

% Free Sulfhydryls

*

*

identification of plasma markers following nov 002 treatment

NOV-002 (25 mg/kg, iv)

0 ¼ ½ 1 4 24 h

Kda

150

100

75

50

37

A

B

C

D

WB: PSSG

WB: actin

Identification of Plasma Markers following NOV-002 treatment

cost recovery system
Cost Recovery System:
  • Assay Development $1,500 + Column
  • PK Modeling $50/ hr
  • Plasma / Serum Assay $50 / sample
  • Organ toxicity analysis $35 / sample
  • Hematology (CBC) $20 / sample
  • GSH/GSSG levels $25 / sample
  • Protein Thiol Analysis $35 / sample
  • Breeze HPLC
    • User Operated Training $ 50 / hour
    • User Operation fee $ 25 / hour
    • Over-night / weekend fee $18 / hour
drug metabolism and pharmacokinetics core16
Drug Metabolism and Pharmacokinetics Core

Drug Discovery Building 420

843-876-2391

Danyelle Townsend, Ph.D., Director Yefim Manevich, Ph.D.,

Drug Discovery Building 420 [email protected]

843-876-2391

[email protected]

Joachim Uys, Ph.D.

PK project manager

[email protected]

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